APPLICANT'S ABSTRACT: This renewal application seeks support to continue research at the Los Angeles Addiction Treatment Research Center. The proposal contains a core and four research components centered on the theme of improving opiate and cocaine pharmacotherapy. The research will be conducted within a consortium of facilities affiliated in varying degrees to UCLA and having overlapping scientific and administrative leadership provided by senior investigators of the LAATRC. The core provides scientific leadership and administrative support, centralized development of research methodology and standardized research procedures for data collection, management, analysis, interpretation and dissemination. An executive committee made up of senior investigators and led by the PI, is aided by an external scientific advisory committee of national prominence. The first component furthers buprenorphine development by testing a three-times-a-week dosing regimen, and explores strategies for buprenorphine discontinuation. Results will provide critical information for buprenorphine's NDA submission. A second component establishes a cost-effective, efficient strategy to evaluate a series of cocaine pharmacotherapy by embedding well-designed controlled clinical trials, with a dose-ranging feature, in a continuous, articulated program which employs standardized study procedures, phases in one medication after another, uses "slots" from early dropouts for subjects in the next study, and reduces down time between trials. Component three will enhance the clinical utility of LAAM by examining take-home doses as a treatment strategy and exploring the use of LAAM in medically compromised addicts. A fourth component examines the relationship of opiate maintenance to pain tolerance and analgesic response to develop better clinical strategies for management of pain associated with acute medical illnesses in opiate maintained patients. The proposed work by the LAATRC will provide critical data for medication development, produce useful information for patient management, provide an enriched environment for training of scientists, and establish the center as a regional and national research resource.